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Neutrophils, reverse traffic and detrimental potential

Cellular & Molecular Immunology volume 9, pages 99–100 (2012)Cite this article

To analyze leukocyte TEM in vivo, Woodfin et al4 built up a four-dimensional imaging system with a relatively high spatial and temporal resolution. With such a powerful imaging system in hand, they found that inflammation mainly triggered paracellular TEM, which could then be divided into normal and disrupted polarized TEM (Figure 1). They also found that disrupted TEM happened mostly under the conditions in which there was lower functional expression of JAM-C at EC junctions. More specifically, they showed that ischemia–reperfusion (I–R), an inflammatory insult that led to significantly lower expression of JAM-C by ECs, was associated with substantial disrupted polarized TEM. Thus, this work provides good evidence to show that EC JAM-C is one of the key regulators mediating the luminal-to-abluminal neutrophil paracellular TEM in vivo.

Until now, one of the main obstacles to directly visualize the migration of leukocytes with high temporal and spatial resolution was the efficient, clear labeling of the EC junction, as the traditional protocol of intravenous administration of fluorescence-labeled monoclonal antibody does not result in a reproducible labeling of ECs for tracking the movement of leukocytes in vivo, Woodfin et al4 have utilized Alexa Fluor555-conjugated monoclonal antibody 390 to platelet/endothelial cell adhesion molecule 1 to label the EC borders. The beauty of this labeling protocol is that it does not inhibit leukocyte transmigration but may result in a strong and reliable labeling of EC borders in cremasteric venules of mice. To elucidate how neutrophils undergo TEM in inflammatory conditions, the authors used proinflammatory cytokine IL-1β, chemotactic formylated tripeptide fMLP, or I–R injury to stimulate the cremaster muscles and mimic the effects of physiological and pathological results on leukocyte TEM. They found that TEM induced by these three stimuli occurred predominantly via the paracellular route rather than the transendothelia route. Notably, their findings suggest that ECs that receive inflammatory stimulation may redistribute their junctional molecules in a way that favors paracellular TEM; however, this is not an altogether surprising result as several studies2, 3, 5 have demonstrated that the paracellular route might be a preferential choice for the TEM of leukocytes.

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Figure 1

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  1. Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

    Gucheng Zeng

  2. Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, IL, USA

    Zheng W. Chen

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  1. Gucheng Zeng
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Correspondence to Gucheng Zeng.

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Zeng, G., Chen, Z. Neutrophils, reverse traffic and detrimental potential. Cell Mol Immunol 9, 99–100 (2012). https://doi.org/10.1038/cmi.2011.33

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